A mesoscopic lattice model for morphology formation in ternary mixtures with evaporation

We develop a mesoscopic lattice model to study the morphology formation in interacting ternary mixtures with the evaporation of one component. As concrete potential application of our model, we wish to capture morphologies as they are typically arising during the fabrication of organic solar cells. In this context, we consider an evaporating solvent into which two other components are dissolved, as a model for a 2-component coating solution that is drying on a substrate. We propose a 3-spins dynamics to describe the evolution of the three interacting species. As main tool, we use a Monte Carlo Metropolis-based algorithm, with the possibility of varying the system's temperature, mixture composition, interaction strengths, and evaporation kinetics. The main novelty is the structure of the mesoscopic model – a bi-dimensional lattice with periodic boundary conditions, divided into square cells to encode a mesoscopic range interaction among the units. We investigate the effect of the model parameters on the structure of the resulting morphologies. Finally, we compare the results obtained with the mesoscopic model with corresponding ones based on an analogous lattice model with a short range interaction among the units, i.e. when the mesoscopic length scale coincides with the microscopic length scale of the lattice

Detection of extended-spectrum β-lactamase and carbapenemase activity in Gram-negative bacilli using liquid chromatography - tandem mass spectrometry

PURPOSE: Several mass spectrometry-based methods for antimicrobial sensitivity testing have been described in recent years. They offer an alternative to commercially available testing systems which were considered to have disadvantages in terms of cost- and time-efficiency. The aim of this study was to develop a LC-MS/MS-based antibiotic hydrolysis assay for evaluating antimicrobial resistance of Gram-negative bacteria. METHODS: Four species of Gram-negative bacilli (Klebsiella pneumoniae, Escherichia coli, Providencia stuartii and Acinetobacter baumannii) were tested against six antibiotics from three different classes: ampicillin, meropenem, imipenem, ceftazidime, ceftriaxone and cefepime. Bacterial suspensions from each species were incubated with a mixture of the six antibiotics. Any remaining antibiotic following incubation were measured using LC-MS/MS. The results were interpreted using measurements obtained for an E. coli strain sensitive to all antibiotics and expressed as percentage of hydrolyzed antibiotic. These were subsequently compared to commercially-available system for the bacteria identification and susceptibility testing. RESULTS: Overall, LC-MS/MS assay and commercial antimicrobial susceptibility platform results showed good agreement in terms of an organism being resistant/sensitive to an antibiotic. The time required to complete the LC-MS/MS-based hydrolysis test was under 5 h, significantly shorter that commercially available susceptibility testing platforms. CONCLUSION: By using a sensitive strain for results interpretation and simultaneous use of multiple antibiotics, the proposed protocol offers improved robustness and multiplexing over previously described methods for antibiotic sensitivity testing. Nevertheless, further research is needed before routine assimilation of the method, especially for strains with intermediate resistance

Members of the KCTD family are major regulators of cAMP signaling

Cyclic adenosine monophosphate (cAMP) is a pivotal second messenger with an essential role in neuronal function. cAMP synthesis by adenylyl cyclases (AC) is controlled by G protein-coupled receptor (GPCR) signaling systems. However, the network of molecular players involved in the process is incompletely defined. Here, we used CRISPR/Cas9-based screening to identify that members of the potassium channel tetradimerization domain (KCTD) family are major regulators of cAMP signaling. Focusing on striatal neurons, we show that the dominant isoform KCTD5 exerts its effects through an unusual mechanism that modulates the influx of Zn2+ via the Zip14 transporter to exert unique allosteric effects on AC. We further show that KCTD5 controls the amplitude and sensitivity of stimulatory GPCR inputs to cAMP production by Gβγ-mediated AC regulation. Finally, we report that KCTD5 haploinsufficiency in mice leads to motor deficits that can be reversed by chelating Zn2+ Together, our findings uncover KCTD proteins as major regulators of neuronal cAMP signaling via diverse mechanisms

The GATA1s isoform is normally down-regulated during terminal haematopoietic differentiation and over-expression leads to failure to repress MYB, CCND2 and SKI during erythroid differentiation of K562 cells

Background: Although GATA1 is one of the most extensively studied haematopoietic transcription factors little is currently known about the physiological functions of its naturally occurring isoforms GATA1s and GATA1FL in humans—particularly whether the isoforms have distinct roles in different lineages and whether they have non-redundant roles in haematopoietic differentiation. As well as being of general interest to understanding of haematopoiesis, GATA1 isoform biology is important for children with Down syndrome associated acute megakaryoblastic leukaemia (DS-AMKL) where GATA1FL mutations are an essential driver for disease pathogenesis. <p/>Methods: Human primary cells and cell lines were analyzed using GATA1 isoform specific PCR. K562 cells expressing GATA1s or GATA1FL transgenes were used to model the effects of the two isoforms on in vitro haematopoietic differentiation. <p/>Results: We found no evidence for lineage specific use of GATA1 isoforms; however GATA1s transcripts, but not GATA1FL transcripts, are down-regulated during in vitro induction of terminal megakaryocytic and erythroid differentiation in the cell line K562. In addition, transgenic K562-GATA1s and K562-GATA1FL cells have distinct gene expression profiles both in steady state and during terminal erythroid differentiation, with GATA1s expression characterised by lack of repression of MYB, CCND2 and SKI. <p/>Conclusions: These findings support the theory that the GATA1s isoform plays a role in the maintenance of proliferative multipotent megakaryocyte-erythroid precursor cells and must be down-regulated prior to terminal differentiation. In addition our data suggest that SKI may be a potential therapeutic target for the treatment of children with DS-AMKL

Exploring synergies between climate and air quality policies using long-term global and regional emission scenarios

In this paper, we present ten scenarios developed using the IMAGE framework (Integrated Model to Assess the Global Environment) to explore how different assumptions on future climate and air pollution policies influence emissions of greenhouse gases and air pollutants. These scenarios describe emission developments in 26 world regions for the 21st century, using a matrix of climate and air pollution policies. For climate policy, the study uses a baseline resulting in forcing levels slightly above RCP6.0 and an ambitious climate policy scenario similar to RCP2.6. For air pollution, the study explores increasingly tight emission standards, ranging from no improvement, current legislation and three variants assuming further improvements. For all pollutants, the results show that more stringent control policies are needed after 2030 to prevent a rise in emissions due to increased activities and further reduce emissions. The results also show that climate mitigation policies have the highest impact on SO2 and NOX emissions, while their impact on BC and OC emissions is relatively low, determined by the overlap between greenhouse gas and air pollutant emission sources. Climate policy can have important co-benefits; a 10% decrease in global CO2 emissions by 2100 leads to a decrease of SO2 and NOX emissions by about 10% and 5%, respectively compared to 2005 levels. In most regions, low levels of air pollutant emissions can also be achieved by solely implementing stringent air pollution policies. The largest differences across the scenarios are found in Asia and other developing regions, where a combination of climate and air pollution policy is needed to bring air pollution levels below those of today

WR 110: A Single Wolf-Rayet Star With Corotating Interaction Regions In Its Wind?

A 30-day contiguous photometric run with the MOST satellite on the WN5-6b star WR 110 (HD 165688) reveals a fundamental periodicity of P = 4.08 +/- 0.55 days along with a number of harmonics at periods P/n, with n ~ 2,3,4,5 and 6, and a few other possible stray periodicities and/or stochastic variability on timescales longer than about a day. Spectroscopic RV studies fail to reveal any plausible companion with a period in this range. Therefore, we conjecture that the observed light-curve cusps of amplitude ~ 0.01 mag that recur at a 4.08 day timescale may arise in the inner parts, or at the base of, a corotating interaction region (CIR) seen in emission as it rotates around with the star at constant angular velocity. The hard X-ray component seen in WR 110 could then be a result of a high velocity component of the CIR shock interacting with the ambient wind at several stellar radii. Given that most hot, luminous stars showing CIRs have two CIR arms, it is possible that either the fundamental period is 8.2 days or, more likely in the case of WR 110, there is indeed a second weaker CIR arm for P = 4.08 days, that occurs ~ two thirds of a rotation period after the main CIR. If this interpretation is correct, WR 110 therefore joins the ranks with three other single WR stars, all WN, with confirmed CIR rotation periods (WR 1, WR 6, and WR 134), albeit with WR 110 having by far the lowest amplitude photometric modulation. This illustrates the power of being able to secure intense, continuous high-precision photometry from space-based platforms such as MOST. It also opens the door to revealing low-amplitude photometric variations in other WN stars, where previous attempts have failed. If all WN stars have CIRs at some level, this could be important for revealing sources of magnetism or pulsation in addition to rotation periods.Comment: 25 pages, 8 figures, 2 tables, accepted in Ap

(So) Big Data and the transformation of the city

The exponential increase in the availability of large-scale mobility data has fueled the vision of smart cities that will transform our lives. The truth is that we have just scratched the surface of the research challenges that should be tackled in order to make this vision a reality. Consequently, there is an increasing interest among different research communities (ranging from civil engineering to computer science) and industrial stakeholders in building knowledge discovery pipelines over such data sources. At the same time, this widespread data availability also raises privacy issues that must be considered by both industrial and academic stakeholders. In this paper, we provide a wide perspective on the role that big data have in reshaping cities. The paper covers the main aspects of urban data analytics, focusing on privacy issues, algorithms, applications and services, and georeferenced data from social media. In discussing these aspects, we leverage, as concrete examples and case studies of urban data science tools, the results obtained in the “City of Citizens” thematic area of the Horizon 2020 SoBigData initiative, which includes a virtual research environment with mobility datasets and urban analytics methods developed by several institutions around Europe. We conclude the paper outlining the main research challenges that urban data science has yet to address in order to help make the smart city vision a reality

Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells

Genome-Wide Characterization of Menin-Dependent H3K4me3 Reveals a Specific Role for Menin in the Regulation of Genes Implicated in MEN1-Like Tumors

Inactivating mutations in the MEN1 gene predisposing to the multiple endocrine neoplasia type 1 (MEN1) syndrome can also cause sporadic pancreatic endocrine tumors. MEN1 encodes menin, a subunit of MLL1/MLL2-containing histone methyltransferase complexes that trimethylate histone H3 at lysine 4 (H3K4me3). The importance of menin-dependent H3K4me3 in normal and transformed pancreatic endocrine cells is unclear. To study the role of menin-dependent H3K4me3, we performed in vitro differentiation of wild-type as well as menin-null mouse embryonic stem cells (mESCs) into pancreatic islet-like endocrine cells (PILECs). Gene expression analysis and genome-wide H3K4me3 ChIP-Seq profiling in wild-type and menin-null mESCs and PILECs revealed menin-dependent H3K4me3 at the imprinted Dlk1-Meg3 locus in mESCs, and all four Hox loci in differentiated PILECs. Specific and significant loss of H3K4me3 and gene expression was observed for genes within the imprinted Dlk1-Meg3 locus in menin-null mESCs and the Hox loci in menin-null PILECs. Given that the reduced expression of genes within the DLK1-MEG3 locus and the HOX loci is associated with MEN1-like sporadic tumors, our data suggests a possible role for menin-dependent H3K4me3 at these genes in the initiation and progression of sporadic pancreatic endocrine tumors. Furthermore, our investigation also demonstrates that menin-null mESCs can be differentiated in vitro into islet-like endocrine cells, underscoring the utility of menin-null mESC-derived specialized cell types for genome-wide high-throughput studies

Accelerated deployment of nanostructured hydrotreating catalysts. Final CRADA Report.

Nanomanufacturing offers an opportunity to create domestic jobs and facilitate economic growth. In response to this need, U.S. Department of Energy, Office of Energy Efficiency and Renewable Energy issued a Research Call to develop nanomanufacturing capabilities at the National Laboratories. High performance catalysts represent a unique opportunity to deploy nanomanufacturing technologies. Re-refining of used lube oil offers an opportunity to create manufacturing jobs and decrease dependence on imported petroleum. Improved catalysts are required to produce a better quality product, decrease environmental impact, extend catalyst life, and improve overall economics of lube oil re-refining. Argonne National Laboratory (Argonne) in cooperation with Universal Lubricants, Inc. (ULI) and Chemical Engineering Partners (CEP) have carried out a Cooperative Research and Development Agreement (CRADA) to prepare nanostructured hydrotreating catalysts using atomic layer deposition (ALD) to exhibit superior performance for the re-refining of used lube oil. We investigated the upgrading of recycled lube oil by hydrogenation using commercial, synthetically-modified commercial catalysts, and synthesized catalysts. A down-flow (trickle bed) catalytic unit was used for the hydrogenation experiments. In addition to carrying out elemental analyses of the various feed and product fractions, characterization was undertaken using H{sup 1} and C{sup 13} NMR. Initially commercial were evaluated. Second these commercial catalysts were promoted with precious metals using atomic layer deposition (ALD). Performance improvements were observed that declined with catalyst aging. An alternate approach was undertaken to deeply upgrade ULI product oils. Using a synthesized catalyst, much lower hydrogenation temperatures were required than commercial catalysts. Other performance improvements were also observed. The resulting lube oil fractions were of high purity even at low reaction severity. The products recovered from both the ALD and other processes were water-white (even those from the low temperature, low residence time (high space velocity), low conversion runs). These results indicate that highly upgraded recycle lube oils can be produced using ALD-deposited active metal catalysts. The use of H{sup 1} and C{sup 13} NMR for the characterization of the treated lube oils has been shown to be effective